Burden of hereditary transthyretin amyloidosis on quality of life.

Introduction: Hereditary transthyretin (hATTR) amyloidosis is a progressive, degenerative disease, with peripheral neuropathy, cardiomyopathy, and other clinical manifestations. In this study we examine the impact of hATTR amyloidosis on quality of life (QOL).

Methods: Neuropathy-specific QOL, measured with the Norfolk QOL-Diabetic Neuropathy questionnaire, was compared between patients with hATTR amyloidosis and patients with type 2 diabetes, whereas generic QOL, measured with the 36-item Short Form Health Survey version 2 (SF-36v2), was compared between patients with hATTR amyloidosis, the general population, and patients with chronic diseases.

Stabilization of amyloidogenic immunoglobulin light chains by small molecules.

In Ig light-chain (LC) amyloidosis (AL), the unique antibody LC protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. As a step toward developing treatments for AL patients with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, we introduce small-molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which can slow or stop the amyloidogenicity cascade at its origin. A protease-coupled fluorescence polarization-based high-throughput screen was employed to identify small molecules that kinetically stabilize LCs.

Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain AL amyloidosis patient.

Systemic light chain amyloidosis (AL)  is a life-threatening disease caused by aggregation and deposition of monoclonal immunoglobulin light chains (LC) in target organs. Severity of heart involvement is the most important factor determining prognosis. Here, we report the 4.

Zebrafish model of amyloid light chain cardiotoxicity: regeneration versus degeneration.

Cardiac dysfunction is the most frequent cause of morbidity and mortality in amyloid light chain (AL) amyloidosis caused by a clonal immunoglobulin light chain (LC). Previously published transgenic animal models of AL amyloidosis have not recapitulated the key phenotype of cardiac dysfunction seen in AL amyloidosis, which has limited our understanding of the disease mechanisms in vivo, as well as the development of targeted AL therapeutics. We have developed a transgenic zebrafish model in which a λ LC derived from a patient with AL amyloidosis is conditionally expressed in the liver under the control of the Gal4 upstream activation sequence enhancer system.

Correction: Assay to rapidly screen for immunoglobulin light chain glycosylation: a potential path to earlier AL diagnosis for a subset of patients.

Following the publication of this article, the authors noted that Patrick M. Vanderboom was inadvertently omitted from the author list. The correct author list is as follows: Sanjay Kumar, David Murray, Surendra Dasari, Paolo Milani, David Barnidge, Benjamin Madden, Patrick M.

ATR-FTIR Spectroscopy Supported by Multivariate Analysis for the Characterization of Adipose Tissue Aspirates from Patients Affected by Systemic Amyloidosis.

Deposition of misfolded proteins as extracellular amyloid aggregates is the pathological hallmark of systemic amyloidoses. Subcutaneous fat acquired by fine needle aspiration is the preferred screening tissue in suspected patients. In this study we employed Fourier transform infrared (FTIR) spectroscopy in attenuated total reflection (ATR) to investigate human abdominal fat aspirates with the aim of detecting disease-related changes in the molecular structure and composition of the tissue and exploiting the potentiality of the method to discriminate between amyloid-positive and -negative samples.

When should treatment of AL amyloidosis start at relapse? Early, to prevent organ progression.

This article has a companion Counterpoint by Sanchorawala.

Improved outcomes for kidney transplantation in AL amyloidosis: impact on practice.

Effective therapies for Ig light chain (AL) amyloidosis has led to an increasing proportion of patients with end-stage renal disease requiring renal replacement therapy, yet kidney transplantation is seldom performed in this setting due to concerns of renal and extrarenal disease progression. Angel-Korman et al. report unprecedented positive long-term outcomes in the largest series of kidney transplantation in AL amyloidosis providing the basis for a more proactive approach to this procedure.

A new genetic variant of hereditary apolipoprotein A-I amyloidosis: a case-report followed by discussion of diagnostic challenges and therapeutic options.

Background: Hereditary amyloidosis refers to a wide spectrum of rare diseases with different causative mutations in the genes of various proteins including transthyretin, apolipoprotein AI and AII, gelsolin, lysozyme, cystatin C, fibrinogen Aα-chain, β2-microglobulin, apolipoprotein CII and CIII.

Case Presentation: Among hereditary amyloidosis subtypes, we describe here a specific case of Apolipoprotein AI amyloidosis (AApoAI), where the diagnosis began from an almost asymptomatic hepatomegaly followed by the development of primary hypogonadism. Baseline laboratory tests showed increased liver enzymes, while imaging tests revealed a suspected infiltrative liver disease.

Publisher Correction: The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group.

In the key to Figure 1 of this article, 'Amyloid microtubules' has been corrected to 'Microtubules'.

The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group.

The term monoclonal gammopathy of renal significance (MGRS) was introduced by the International Kidney and Monoclonal Gammopathy Research Group (IKMG) in 2012. The IKMG met in April 2017 to refine the definition of MGRS and to update the diagnostic criteria for MGRS-related diseases. Accordingly, in this Expert Consensus Document, the IKMG redefines MGRS as a clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin and does not meet previously defined haematological criteria for treatment of a specific malignancy.

Systemic immunoglobulin light chain amyloidosis.

Systemic immunoglobulin light chain amyloidosis is a protein misfolding disease caused by the conversion of immunoglobulin light chains from their soluble functional states into highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac damage and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the detection and quantification of organ involvement and damage is facilitating earlier diagnosis and improved evaluation of the efficacy of new and existing therapies.

Development and validation of a survival staging system incorporating BNP in patients with light chain amyloidosis.

Immunoglobulin light chain amyloidosis (AL amyloidosis) is caused by misfolded light chains that form soluble toxic aggregates that deposit in tissues and organs, leading to organ dysfunction. The leading determinant of survival is cardiac involvement. Current staging systems use -terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins T and I (TnT and TnI) for prognostication, but many centers do not offer NT-proBNP.

Lymphocyte activation gene 3 (Lag3) expression is increased in prion infections but does not modify disease progression.

Prion diseases, Alzheimer's disease and Parkinson's disease (PD) are fatal degenerative disorders that share common neuropathological and biochemical features, including the aggregation of pathological protein conformers. Lymphocyte activation gene 3 (Lag3, also known as CD223) is a member of the immunoglobulin superfamily of receptors expressed on peripheral immune cells, microglia and neurons, which serves as a receptor for α-synuclein aggregates in PD. Here we examined the possible role of Lag3 in the pathogenesis of prion diseases.